TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14173	42742;42743;42744	chr2:178633982;178633981;178633980	chr2:179498709;179498708;179498707
N2AB	12532	37819;37820;37821	chr2:178633982;178633981;178633980	chr2:179498709;179498708;179498707
N2A	11605	35038;35039;35040	chr2:178633982;178633981;178633980	chr2:179498709;179498708;179498707
N2B	5108	15547;15548;15549	chr2:178633982;178633981;178633980	chr2:179498709;179498708;179498707
Novex-1	5233	15922;15923;15924	chr2:178633982;178633981;178633980	chr2:179498709;179498708;179498707
Novex-2	5300	16123;16124;16125	chr2:178633982;178633981;178633980	chr2:179498709;179498708;179498707
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-92
• Domain position: 32
• Structural Position: 47
• Q(SASA): 0.2192
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/A	None	None	0.019	N	0.323	0.058	0.506068822696	gnomAD-4.0.0	5.47485E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87273E-05	0	6.2975E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.1182	likely_benign	0.1289	benign	-1.928	Destabilizing	0.019	N	0.323	neutral	N	0.492626104	None	None	N
V/C	0.6253	likely_pathogenic	0.6198	pathogenic	-0.993	Destabilizing	0.667	D	0.502	neutral	None	None	None	None	N
V/D	0.1932	likely_benign	0.246	benign	-2.392	Highly Destabilizing	0.175	N	0.527	neutral	N	0.502715164	None	None	N
V/E	0.161	likely_benign	0.2133	benign	-2.25	Highly Destabilizing	0.055	N	0.465	neutral	None	None	None	None	N
V/F	0.1578	likely_benign	0.1357	benign	-1.292	Destabilizing	0.602	D	0.537	neutral	N	0.510762249	None	None	N
V/G	0.1857	likely_benign	0.1965	benign	-2.352	Highly Destabilizing	0.042	N	0.446	neutral	N	0.508827218	None	None	N
V/H	0.3391	likely_benign	0.3717	ambiguous	-2.013	Highly Destabilizing	0.667	D	0.543	neutral	None	None	None	None	N
V/I	0.08	likely_benign	0.0762	benign	-0.772	Destabilizing	0.042	N	0.46	neutral	N	0.49177538	None	None	N
V/K	0.2184	likely_benign	0.2372	benign	-1.626	Destabilizing	None	N	0.343	neutral	None	None	None	None	N
V/L	0.1448	likely_benign	0.1387	benign	-0.772	Destabilizing	0.019	N	0.342	neutral	N	0.478735164	None	None	N
V/M	0.1222	likely_benign	0.1095	benign	-0.486	Destabilizing	0.667	D	0.493	neutral	None	None	None	None	N
V/N	0.1377	likely_benign	0.1498	benign	-1.656	Destabilizing	0.124	N	0.527	neutral	None	None	None	None	N
V/P	0.7285	likely_pathogenic	0.7843	pathogenic	-1.131	Destabilizing	0.364	N	0.525	neutral	None	None	None	None	N
V/Q	0.1766	likely_benign	0.2103	benign	-1.665	Destabilizing	0.22	N	0.538	neutral	None	None	None	None	N
V/R	0.2072	likely_benign	0.2209	benign	-1.258	Destabilizing	0.124	N	0.551	neutral	None	None	None	None	N
V/S	0.1063	likely_benign	0.1181	benign	-2.157	Highly Destabilizing	None	N	0.329	neutral	None	None	None	None	N
V/T	0.0885	likely_benign	0.0956	benign	-1.906	Destabilizing	None	N	0.176	neutral	None	None	None	None	N
V/W	0.7271	likely_pathogenic	0.7023	pathogenic	-1.741	Destabilizing	0.958	D	0.553	neutral	None	None	None	None	N
V/Y	0.403	ambiguous	0.3991	ambiguous	-1.371	Destabilizing	0.667	D	0.541	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.